Prospective Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2024; 30(11): 1572-1587
Published online Mar 21, 2024. doi: 10.3748/wjg.v30.i11.1572
Washed microbiota transplantation for Crohn’s disease: A metagenomic, metatranscriptomic, and metabolomic-based study
Shi-Ju Chen, Da-Ya Zhang, Xia Wu, Fa-Ming Zhang, Bo-Ta Cui, Yi-Hao Huang, Zu-Lun Zhang, Rui Wang, Fei-Hu Bai
Shi-Ju Chen, Da-Ya Zhang, Graduate School, Hainan Medical University, Haikou 571199, Hainan Province, China
Xia Wu, Fa-Ming Zhang, Bo-Ta Cui, Yi-Hao Huang, Zu-Lun Zhang, Rui Wang, Department of Microbiota Medicine & Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China
Fei-Hu Bai, Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, Haikou 570216, Hainan Province, China
Co-first authors: Shi-Ju Chen and Da-Ya Zhang.
Author contributions: Chen SJ and Zhang DY contributed equally to this work; Chen SJ, Zhang DY, Wu X, Zhang FM, Cui BT, and Bai FH participated in the design of this study and performed the statistical analysis; Chen SJ, Zhang DY, Wu X, and Bai FH drafted the manuscript; Huang YH, Zhang ZL and Wang R recruited participants and participated in the data collection; all authors read and approved the final manuscript.
Supported by the Innovation Platform for Academicians of Hainan Province, No. YSPTZX202313; Hainan Province Clinical Medical Center, No. 2021818; Hainan Provincial Health Industry Research Project, No. 22A200078; Hainan Provincial Postgraduate Innovation Research Project, No. Qhyb2022-133; Hainan Medical University Graduate Student Innovative Research Project, No. HYYB2022A18; and Nanjing Medical University Fan Daiming Research Funds for Holistic Integrative Medicine, No. 2020-3HIM.
Institutional review board statement: The study was reviewed and approved by the Second Affiliated Hospital of Nanjing Medical University Institutional Review Board [Approval No. (2022-KY-161-01)].
Clinical trial registration statement: This study is registered at ClinicalTrials.gov. The registration identification number is NCT01793831.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Zhang FM conceived the concept of GenFMTer and transendoscopic enteral tubing and devices related to them; the remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Data sharing statement: The datasets generated and/or analysed during the current study are available in the NCBI BioProject database (PRJNA1069244) and MetaboLights repository (MTBLS9421).
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Fei-Hu Bai, PhD, Chief Doctor, Professor, Department of Gastroenterology, The Second Affiliated Hospital of Hainan Medical University, No. 368 Yehai Avenue, Longhua District, Haikou 570216, Hainan Province, China. baifeihu_hy@163.com
Received: January 7, 2024
Peer-review started: January 7, 2024
First decision: February 1, 2024
Revised: February 7, 2024
Accepted: March 6, 2024
Article in press: March 6, 2024
Published online: March 21, 2024
Processing time: 74 Days and 0 Hours
ARTICLE HIGHLIGHTS
Research background

Incidence of Crohn’s disease (CD) is increasing every year, posing a serious threat to human health. Fecal microbial transplantation (FMT) is a promising therapeutic approach for the treatment of CD. The new methodology of FMT, based on the automatic washing process, was named as washed microbiota transplantation (WMT).

Research motivation

Most existing studies have focused on observing clinical phenomena. However, a combined multi-omics (metagenomic, metatranscriptomic, and metabolomic) analysis of FMT for the effective treatment of CD has not been reported.

Research objectives

To examine the effects of two consecutive fixed WMT doses on clinical and endoscopic outcomes in CD patients. A secondary aim was to explore alterations in the microbiome and metabolome in response to WMT.

Research methods

WMT was administered to 11 patients with active CD. Their clinical response (defined as a decrease in CD activity index score > 100 points) was assessed three months after transplantation. Fecal samples collected 1 wk before and 3 months after WMT were subjected to combined metagenomic, metatranscriptomic, and metabolomic analyses.

Research results

Seven of 11 patients (63.6%) demonstrated response 3 months after WMT. There was a significant increase in the diversity of the gut microbiota after WMT, consistent with improved clinical symptoms. A comparison of metagenomic and metatranscriptomic analyses revealed constant changes in certain strains, such as Faecalibacterium prausnitzii, Roseburia intestinalis, and Escherichia coli. Metabolomic analysis of the responder group identified certain amino acids that may be associated with disease progression (e.g., L-glutamic acid, gamma-glutamyl-leucine, and prolyl-glutamine) that were higher in the pre-transplant than in the donor but lower in the post-transplant.

Research conclusions

WMT has shown efficacy in CD treatment, possibly due to the effective reconstitution of the patient’s microbiome. Combined metagenomic, metatranscriptomic, and metabolomic analyses can effectively help decipher the underlying mechanisms of WMT for CD.

Research perspectives

The exact mechanism by which FMT treats CD still needs to be better understood. Future studies need to clarify the underlying mechanisms by utilizing additional histological techniques (e.g., macro-proteomics and culture genomics etc.).